The mechanism of death during gram-negative endotoxin or septic shock is not known. This deficiency in our knowledge is basically responsible for the lack of an effective therapeutic procedure and high mortality during this condition. Although a causal relationship between arterial hypoglycemia and mortality has been proposed, the mechanism of hypoglycemia is unknown. The overall objective of the proposed research is to determine the peripheral mechanism of the hypoglycemia and to identify the major peripheral organ(s) involved. The basic hypothesis to be tested is that an increased uptake of glucose by skeletal muscle contributes to the hypoglycemia of shock. Secondary hypotheses to be tested are that glucose uptake is increased in adipose tissue or skin during shock. Anesthesized, heparinized mongrel dog and baboons will be used. The isolated, perfused gracilis muscle will be the basic preparation. Experiments will also be completed using isolated forelimb and isolated adipose tissue preparations. A number of vascular and metabolic parameters will be determined before and during shock induced by endotoxin or live E. coli bacterial intravenous infusions. Both acute and chronic experiments will be completed. These data will be compared to those obtained during hemorrhagic shock. This project will provide additional data relative to mechanisms of death during shock, with specific reference to changes in peripheral utilization of glucose, and will aid in the development of an effective therapeutic procedure during circulatory shock.